title: Delayed lymphoid repopulation with defects in IL-4-driven responses produced by inactivation of NF-ATc.
abstract: The NF-AT family of transcription factors activates early immune response genes such as cytokines. In the adult, NF-ATc is expressed exclusively in the lymphoid system and is induced upon lymphocyte activation. NF-ATc null mutant mice die in utero of cardiac failure, precluding analysis of the role of NF-ATc in lymphocyte activation. By using RAG-2-deficient blastocyst complementation, we now demonstrate that young, highly chimeric mice lacking NF-ATc have impaired repopulation of both thymus and peripheral lymphoid organs. Furthermore, NF-ATc deficiency impaired T lymphocyte activation and secretion of IL-4. B lymphocytes displayed reduced proliferation and a selective loss of IL-4-driven immunoglobulin isotypes both in vivo and in vitro. Our data demonstrate that NF-ATc is essential for the optimal generation and function of mature T and B lineage cells, with an especially profound effect on IL-4-driven responses.
authors.affiliation: Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Ranger
authors.forename: M R
authors.initials: MR
authors.lastname: Hodge
authors.forename: E M
authors.initials: EM
authors.lastname: Gravallese
authors.forename: M
authors.initials: M
authors.lastname: Oukka
authors.forename: L
authors.initials: L
authors.lastname: Davidson
authors.forename: F W
authors.initials: FW
authors.lastname: Alt
authors.forename: F C
authors.initials: FC
authors.lastname: de la Brousse
authors.forename: T
authors.initials: T
authors.lastname: Hoey
authors.forename: M
authors.initials: M
authors.lastname: Grusby
authors.forename: L H
authors.initials: LH
authors.lastname: Glimcher
mesh_terms: D000483:Alleles; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000502:physiology*; D008099:Liver / Q000196:embryology / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; C499308:Rag2 protein, mouse; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C064655:V(D)J recombination activating protein 2; D015847:Interleukin-4; D007073:Immunoglobulin E